TY - JOUR

T1 - Quantitative genome-wide association analyses of receptive language in the Danish High Risk and Resilience Study

AU - Nudel, Ron

AU - Christiani, Camilla A.J.

AU - Ohland, Jessica

AU - Uddin, Md Jamal

AU - Hemager, Nicoline

AU - Ellersgaard, Ditte

AU - Spang, Katrine S.

AU - Burton, Birgitte K.

AU - Greve, Aja N.

AU - Gantriis, Ditte L.

AU - Bybjerg-Grauholm, Jonas

AU - Jepsen, Jens Richardt M.

AU - Thorup, Anne A.E.

AU - Mors, Ole

AU - Werge, Thomas

AU - Nordentoft, Merete

PY - 2020

Y1 - 2020

N2 - Background: One of the most basic human traits is language. Linguistic ability, and disability, have been shown to have a strong genetic component in family and twin studies, but molecular genetic studies of language phenotypes are scarce, relative to studies of other cognitive traits and neurodevelopmental phenotypes. Moreover, most genetic studies examining such phenotypes do not incorporate parent-of-origin effects, which could account for some of the heritability of the investigated trait. We performed a genome-wide association study of receptive language, examining both child genetic effects and parent-of-origin effects. Results: Using a family-based cohort with 400 children with receptive language scores, we found a genome-wide significant paternal parent-of-origin effect with a SNP, rs11787922, on chromosome 9q21.31, whereby the T allele reduced the mean receptive language score by ~ 23, constituting a reduction of more than 1.5 times the population SD (P = 1.04 × 10-8). We further confirmed that this association was not driven by broader neurodevelopmental diagnoses in the child or a family history of psychiatric diagnoses by incorporating covariates for the above and repeating the analysis. Conclusions: Our study reports a genome-wide significant association for receptive language skills; to our knowledge, this is the first documented genome-wide significant association for this phenotype. Furthermore, our study illustrates the importance of considering parent-of-origin effects in association studies, particularly in the case of cognitive or neurodevelopmental traits, in which parental genetic data are not always incorporated.

AB - Background: One of the most basic human traits is language. Linguistic ability, and disability, have been shown to have a strong genetic component in family and twin studies, but molecular genetic studies of language phenotypes are scarce, relative to studies of other cognitive traits and neurodevelopmental phenotypes. Moreover, most genetic studies examining such phenotypes do not incorporate parent-of-origin effects, which could account for some of the heritability of the investigated trait. We performed a genome-wide association study of receptive language, examining both child genetic effects and parent-of-origin effects. Results: Using a family-based cohort with 400 children with receptive language scores, we found a genome-wide significant paternal parent-of-origin effect with a SNP, rs11787922, on chromosome 9q21.31, whereby the T allele reduced the mean receptive language score by ~ 23, constituting a reduction of more than 1.5 times the population SD (P = 1.04 × 10-8). We further confirmed that this association was not driven by broader neurodevelopmental diagnoses in the child or a family history of psychiatric diagnoses by incorporating covariates for the above and repeating the analysis. Conclusions: Our study reports a genome-wide significant association for receptive language skills; to our knowledge, this is the first documented genome-wide significant association for this phenotype. Furthermore, our study illustrates the importance of considering parent-of-origin effects in association studies, particularly in the case of cognitive or neurodevelopmental traits, in which parental genetic data are not always incorporated.

KW - Danish High Risk and Resilience Study

KW - Genetics

KW - GWAS

KW - Linguistics

KW - Parent-of-origin

KW - Receptive language

U2 - 10.1186/s12868-020-00581-5

DO - 10.1186/s12868-020-00581-5

M3 - Journal article

C2 - 32635940

AN - SCOPUS:85087725531

VL - 21

JO - B M C Neuroscience

JF - B M C Neuroscience

SN - 1471-2202

M1 - 30

ER -